Top POEMs of 2015: Diabetes Mellitus

Top 20 POEMs of 2015

In T2DM, Intensive Glucose Control Modestly Reduces CV Events, but Not Mortality, After 10 Years

Clinical question
Are there long-term benefits to more intensive glycemic control in patients with type 2 diabetes mellitus?

Bottom line
After approximately 10 years of follow-up, this study found 1 fewer cardiovascular event per 116 person-years among a group of patients (97% men) randomized to receive tight glycemic control, but found no reduction in mortality. This result must be balanced against the results from other trials, which saw a mixed bag of benefits and harms with long-term follow-up. It is important to note that even the intensive glycemic control group had a mean hemoglobin A1c of 6.9%, not 6% or 6.5% as some guidelines advocate. (LOE = 2b)(www.essentialevidenceplus.com)

Reference
Hayward RA, Reaven PD, Wiitala WL, et al, for the VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;372(23):2197-2206.

Study design: Cohort (prospective)

Funding source: Government

Setting: Outpatient (any)

Synopsis
The Veteran's Affairs Diabetes Trial (VADT) originally randomized 1791 veterans with type 2 diabetes mellitus to receive intensive or usual glycemic control, and achieved mean hemoglobin A1C levels of 6.9% and 8.4%, respectively, after a median of 5.6 years. The original trial found a nonsignificant trend toward fewer cardiovascular events in the intensive therapy group, but no change in mortality. Two other large, similar trials reported similar findings, although one found increased mortality in the intensive glycemic control group. Follow-up studies for these 2 other trials have had mixed results, one finding increased mortality and no change in events, with the other finding fewer events but no change in mortality. The current study linked patients in the original VADT to national disease registries (92% of participants) and also to regular record reviews and surveys (77% agreed to participte). The median follow-up was 9.8 years for cardiovascular events and 11.8 years for assessment of total mortality. They found a small but statistically significant reduction in the primary combined outcome of myocardial infarction , stroke, new or worsening heart failure, cardiovascular death, or amputation (44.1 vs 52.7 per 1000 person-years; P = .04). There was no significant difference between groups in the likelihood of cardiovascular death or all-cause mortality. The greatest contribution to the reduction in cardiovascular events was fewer nonfatal myocardial infarctions.

Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA

Tight Glycemic Control Doesn't Decrease Ischemic Heart Disease Events (ACCORD)

Clinical question
Does intensive glycemic control in high-risk patients with type 2 diabetes decrease the frequency of ischemic heart disease events?

Bottom line
Intensive glycemic control compared with usual care doesn't reduce the rate of ischemic heart disease events. As demonstrated in multiple studies, an elevated glucose level in a patient with type 2 diabetes is a risk factor for bad outcomes, but lowering the glucose level does nothing meaningful other than lowering the glucose level. (LOE = 2a-)(www.essentialevidenceplus.com)

Reference
Gerstein HC, Miller ME, Ismail-Beigi F, et al, for the ACCORD Study Group. Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet 2014;384(9958):1936-1941.

Funding source: Government

Synopsis
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial (www.essentialevidenceplus.com/content/poem/100825; www.essentialevidenceplus.com/content/poem/130503) randomized more than 10,000 men and women aged 40 to 79 years with type 2 diabetes and known cardiovascular disease or cardiovascular risk factors to either intensive glucose control (glycated hemoglobin target: < 6.0%) or usual control (target: 7.0% - 7.9%). The intensive control part of the trial, although demonstrating a decrease in the rate on nonfatal myocardial infarctions, was terminated early because of excess mortality in the patients assigned to intensive control. The study team decided to continue following the patients for the remainder of the study period. So this becomes a difficult design to evaluate — for the first 3.7 years, some patients received intensive treatment and some received usual care, but for the last 18 months of the study, everybody was treated the same. This is probably best considered as a secondary analysis of the ACCORD Trial and therefore better at generating hypotheses than answering them. Nonetheless, the authors report slight reductions in the rate of the combined outcome of myocardial infarction, revascularization, and unstable angina; when adjusting for glycated hemoglobin concentration over time, however, all differences went away. Since the original study was a major downer for the ACCORD team and for those who still want to promote tight glycemic control in patients with type 2 diabetes, these authors report on a secondary analysis of what happened after the intensive treatment was halted. In other words, this was really a thinly disguised attempt to salvage something out of the failed ACCORD Trial. The only thing they found has already been demonstrated in too many studies to count: An elevated glucose level in a patient with type 2 diabetes is a risk factor for bad outcomes, but lowering the glucose level does nothing other than lowering the glucose level.

Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI

Glycemic Control Associated with Better Outcomes in Patients with T1DM

Clinical question
What is the association between glycemic control and cardiovascular mortality in patients with type 1 diabetes mellitus?

Bottom line
This study finds a strong association between glycemic control and cardiovascular events in patients with type1 diabetes mellitus (T1DM). It also finds a strong association between the presence of T1DM and earlier mortality. Poor glycemic control is associated with worsening. (LOE = 2b)(www.essentialevidenceplus.com)

Reference
Lind M, Svensson AM, Kosiborod M, et al. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med 2014;371(21):1972-1982.

Study design: Cohort (prospective)

Funding source: Industry + govt

Setting: Population-based

Synopsis
This Swedish study used data from a national registry of patients with T1DM, defined as disease onset before the age of 30 years and requiring insulin. The registry tracks medications, complications, and risk factors among adults with T1DM. These researchers included everyone in the register in 1998 and followed them through the end of 2011 (or until the patient died). They also identified 5 control patients from the same county matched to each case by age and sex. Participants were followed up for a mean of approximately 8 years. The researchers divided patients with T1DM into quintiles by glycated hemoglobin control, from less than or equal to 6.9% to greater than or equal to 9.7%. Patients with worse glycemic control also tended to have higher levels of low density lipoprotein cholesterol and higher rates of tobacco use (8.9% in the lowest quintile to 23.4% in the highest). A series of Cox regression models were created, with successive models incorporating more potential confounders. In the fully adjusted model, cardiovascular mortality increased with increasing levels of glycohemoglobin, with a relative risk of 2.43 (95% CI 1.7-3.4) for the highest compared with the lowest quintiles. The likelihood of death from cardiovascular disease was significantly higher in patients with T1DM than in control patients, even for those with excellent glycemic control.

Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA

POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).

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